Highly efficient free-breathing 3D whole-heart imaging in 3-min: single center study in adults with congenital heart disease.

BACKGROUND: Three dimensional, whole-heart (3DWH) MRI is an established non-invasive imaging modality in patients with congenital heart disease (CHD) for the diagnosis of cardiovascular morphology and for clinical decision making. Current techniques utilise diaphragmatic navigation (dNAV) for respiratory motion correction and gating and are frequently limited by long acquisition times. This study proposes and evaluates the diagnostic performance of a respiratory gating-free framework, which considers respiratory image-based navigation (iNAV), and highly accelerated variable density Cartesian sampling in concert with non-rigid motion correction and low-rank patch-based denoising (iNAV-3DWH-PROST). The method is compared to the clinical dNAV-3DWH sequence in adult patients with CHD. METHODS: In this prospective single center study, adult patients with CHD who underwent the clinical dNAV-3DWH MRI were also scanned with the iNAV-3DWH-PROST. Diagnostic confidence (4-point Likert scale) and diagnostic accuracy for common cardiovascular lesions was assessed by three readers. Scan times and diagnostic confidence were compared using the Wilcoxon-signed rank test. Co-axial vascular dimensions at three anatomic landmarks were measured, and agreement between the research and the corresponding clinical sequence was assessed with Bland-Altman analysis. RESULTS: The study included 60 participants (mean age ± [SD]: 33 ± 14 years; 36 men). The mean acquisition time of iNAV-3DWH-PROST was significantly lower compared with the conventional clinical sequence (3.1 ± 0.9 min vs 13.9 ± 3.9 min, p < 0.0001). Diagnostic confidence was higher for the iNAV-3DWH-PROST sequence compared with the clinical sequence (3.9 ± 0.2 vs 3.4 ± 0.8, p < 0.001), however there was no significant difference in diagnostic accuracy. Narrow limits of agreement and mean bias less than 0.08 cm were found between the research and the clinical vascular measurements. CONCLUSIONS: The iNAV-3DWH-PROST framework provides efficient, high quality and robust 3D whole-heart imaging in significantly shorter scan time compared to the standard clinical sequence.

Differential Detection of Hepatic Metastases on 68 Ga-DOTATATE PET/CT and 177 Lu-DOTATATE SPECT/CT.

ABSTRACT: 68 Ga-DOTATATE PET/CT is indicated for selecting patients for peptide receptor radionuclide therapy (PRRT). Although highly sensitive, the detectability of smaller lesions, particularly in the liver, is lower. We present the case of a 58-year-old man with metastatic well-differentiated pancreatic neuroendocrine tumor whose MRI revealed progression of hepatic metastases. 68 Ga-DOTATATE PET/CT performed to determine eligibility for PRRT did not demonstrate DOTATATE-avid disease within the liver. 18 F-FDG PET/CT was also negative at the liver and the patient proceeded to 177 Lu-DOTATATE PRRT, where multi-time point posttherapy planar imaging and SPECT/CT showed intense uptake in the known liver metastases.

Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction.

Importance: Coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may contribute to the pathophysiologic characteristics of heart failure with preserved ejection fraction (HFpEF). However, the prevalence of CAD and CMD have not been systematically studied. Objective: To examine the prevalence of CAD and CMD in hospitalized patients with HFpEF. Design, Setting, and Participants: A total of 106 consecutive patients hospitalized with HFpEF were evaluated in this prospective, multicenter, cohort study conducted between January 2, 2017, and August 1, 2018; data analysis was performed from March 4 to September 6, 2019. Participants underwent coronary angiography with guidewire-based assessment of coronary flow reserve, index of microvascular resistance, and fractional flow reserve, followed by coronary vasoreactivity testing. Cardiac magnetic resonance imaging was performed with late gadolinium enhancement and assessment of extracellular volume. Myocardial perfusion was assessed qualitatively and semiquantitatively using the myocardial-perfusion reserve index. Main Outcomes and Measures: The prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis. Results: Of 106 participants enrolled (53 [50%] women; mean [SD] age, 72 [9] years), 75 had coronary angiography, 62 had assessment of coronary microvascular function, 41 underwent coronary vasoreactivity testing, and 52 received cardiac magnetic resonance imaging. Obstructive epicardial CAD was present in 38 of 75 participants (51%, 95% CI, 39%-62%); 19 of 38 (50%; 95% CI, 34%-66%) had no history of CAD. Endothelium-independent CMD (ie, coronary flow reserve <2.0 and/or index of microvascular resistance ≥25) was identified in 41 of 62 participants (66%; 95% CI, 53%-77%). Endothelium-dependent CMD (ie, abnormal coronary vasoreactivity) was identified in 10 of 41 participants (24%; 95% CI, 13%-40%). Overall, 45 of 53 participants (85%; 95% CI, 72%-92%) had evidence of CMD and 29 of 36 (81%; 95% CI, 64%-91%) of those without obstructive epicardial CAD had CMD. Cardiac magnetic resonance imaging findings included myocardial-perfusion reserve index less than or equal to 1.84 (ie, impaired global myocardial perfusion) in 29 of 41 patients (71%; 95% CI, 54%-83%), visual perfusion defect in 14 of 46 patients (30%; 95% CI, 19%-46%), ischemic late gadolinium enhancement (ie, myocardial infarction) in 14 of 52 patients (27%; 95% CI, 16%-41%), and extracellular volume greater than 30% (ie, diffuse myocardial fibrosis) in 20 of 48 patients (42%; 95% CI, 28%-56%). Patients with obstructive CAD had more adverse events during follow-up (28 [74%]) than those without obstructive CAD (17 [46%]). Conclusions and Relevance: In this cohort study, 91% of patients with HFpEF had evidence of epicardial CAD, CMD, or both. Of those without obstructive CAD, 81% had CMD. Obstructive epicardial CAD and CMD appear to be common and often unrecognized in hospitalized patients with HFpEF and may be therapeutic targets.

1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA).

OBJECTIVES: The aim of this study was to test the hypothesis that invasive coronary function testing at time of angiography could help stratify management of angina patients without obstructive coronary artery disease. BACKGROUND: Medical therapy for angina guided by invasive coronary vascular function testing holds promise, but the longer-term effects on quality of life and clinical events are unknown among patients without obstructive disease. METHODS: A total of 151 patients with angina with symptoms and/or signs of ischemia and no obstructive coronary artery disease were randomized to stratified medical therapy guided by an interventional diagnostic procedure versus standard care (control group with blinded interventional diagnostic procedure results). The interventional diagnostic procedure-facilitated diagnosis (microvascular angina, vasospastic angina, both, or neither) was linked to guideline-based management. Pre-specified endpoints included 1-year patient-reported outcome measures (Seattle Angina Questionnaire, quality of life [EQ-5D]) and major adverse cardiac events (all-cause mortality, myocardial infarction, unstable angina hospitalization or revascularization, heart failure hospitalization, and cerebrovascular event) at subsequent follow-up. RESULTS: Between November 2016 and December 2017, 151 patients with ischemia and no obstructive coronary artery disease were randomized (n = 75 to the intervention group, n = 76 to the control group). At 1 year, overall angina (Seattle Angina Questionnaire summary score) improved in the intervention group by 27% (difference 13.6 units; 95% confidence interval: 7.3 to 19.9; p < 0.001). Quality of life (EQ-5D index) improved in the intervention group relative to the control group (mean difference 0.11 units [18%]; 95% confidence interval: 0.03 to 0.19; p = 0.010). After a median follow-up duration of 19 months (interquartile range: 16 to 22 months), major adverse cardiac events were similar between the groups, occurring in 9 subjects (12%) in the intervention group and 8 (11%) in the control group (p = 0.803). CONCLUSIONS: Stratified medical therapy in patients with ischemia and no obstructive coronary artery disease leads to marked and sustained angina improvement and better quality of life at 1 year following invasive coronary angiography. (Coronary Microvascular Angina [CorMicA]; NCT03193294).

Ischemia and No Obstructive Coronary Artery Disease: Prevalence and Correlates of Coronary Vasomotion Disorders.

BACKGROUND: Determine the prevalence and correlates of microvascular and vasospastic angina in patients with symptoms and signs of ischemia but no obstructive coronary artery disease (INOCA). METHODS: Three hundred ninety-one patients with angina were enrolled at 2 regional centers over 12 months from November 2016 (NCT03193294). INOCA subjects (n=185; 47%) had more limiting dyspnea (New York Heart Association classification III/IV 54% versus 37%; odds ratio [OR], 2.0 [1.3-3.0]; P=0.001) and were more likely to be female (68% INOCA versus 38% in coronary artery disease; OR, 1.9 [1.5 to 2.5]; P<0.001) but with lower cardiovascular risk scores (ASSIGN score median 20% versus 24%; P=0.003). INOCA subjects had similar burden of angina (Seattle Angina Questionnaire) but reduced quality of life compared with coronary artery disease; subjects (EQ5D-5 L index 0.60 versus 0.65 units; P=0.041). RESULTS: An interventional diagnostic procedure with reference invasive tests including coronary flow reserve, microvascular resistance, and vasomotor responses to intracoronary acetylcholine (vasospasm provocation) was performed in 151 INOCA subjects. Overall, 78 (52%) had isolated microvascular angina, 25 (17%) had isolated vasospastic angina, 31 (20%) had both, and 17 (11%) had noncardiac chest pain. Regression analysis showed inducible ischemia on treadmill testing (OR, 7.5 [95% CI, 1.7-33.0]; P=0.008) and typical angina (OR, 2.7 [1.1-6.6]; P=0.032) were independently associated with microvascular angina. Female sex tended to associate with a diagnosis of microvascular angina although this was not significant (OR, 2.7 [0.9-7.9]; P=0.063). Vasospastic angina was associated with smoking (OR, 9.5 [2.8-32.7]; P<0.001) and age (OR, 1.1 per year, [1.0-1.2]; P=0.032]. CONCLUSIONS: Over three quarters of patients with INOCA have identifiable disorders of coronary vasomotion including microvascular and vasospastic angina. These patients have comparable angina burden but reduced quality of life compared to patients with obstructive coronary artery disease. Microvascular angina and vasospastic angina are distinct disorders that may coexist but differ in associated clinical characteristics, symptoms, and angina severity. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03193294.

Improving medication optimisation in left ventricular systolic dysfunction after acute myocardial infarction.

Glasgow city has the highest cardiovascular disease (CVD) mortality rate in the UK. Patients with left ventricular systolic dysfunction after acute myocardial infarction represent a 'high-risk' cohort for adverse CVD outcomes. The optimisation of secondary prevention medication in this group is often suboptimal. Our aim was to improve the use and target dosing of ACE inhibitors (ACEI), angiotensin II receptor blockers (ARBs) and beta-blockers in such patients, through pharmacist-led clinics and cardiology multidisciplinary team collaboration. Retrospective audits characterised baseline care. Prospective pharmacist-led clinics were piloted and rolled out across seven hospitals and primary care localities over four Plan-Do-Study-Act cycles. 'Hub' and 'spoke' clinics utilised independent prescribing pharmacists with different levels of cardiology experience. Pharmacists were trained through a bespoke training programme-'Teach and Treat'. Consultant cardiologists provided senior support and governance. Patients attending prospective pharmacist-led clinics were more likely to be prescribed an ACEI (or ARB) and beta-blocker (n=856/885 (97%) vs n=233/255 (91%), p<0.001 and n=813/885 (92%) vs n=224/255 (88%), p=0.048, respectively) and be on target dose of ACEI (or ARB) and beta-blocker (n=585/885 (66%) vs n=64/255 (25%), p<0.001 and n=218/885 (25%) vs n=17/255 (7%), p<0.001, respectively) compared with baseline. The mean dose of ACEI (or ARB) and beta-blocker was also higher (79% vs 48% of target dose, p<0.001% and 48% vs 33% of target dose, p<0.001, respectively) compared with baseline. Use of secondary prevention medication was significantly improved by pharmacist and cardiology collaboration. These improvements were sustained across a 4-year period, supported by a novel approach called 'Teach and Treat' which linked training to defined clinical service delivery. Further work is needed to assess the impact of the programme on long-term CVD outcomes.

Predictors of segmental myocardial functional recovery in patients after an acute ST-Elevation myocardial infarction.

OBJECTIVE: We hypothesized that Displacement Encoding with Stimulated Echoes (DENSE) and feature-tracking derived circumferential strain would provide incremental prognostic value over the extent of infarction for recovery of segmental myocardial function. METHODS: Two hundred and sixty-one patients (mean age 59 years, 73% male) underwent MRI 2 days post-ST elevation myocardial infarction (STEMI) and 241 (92%) underwent repeat imaging 6 months later. The MRI protocol included cine, 2D-cine DENSE, T2 mapping and late enhancement. Wall motion scoring was assessed by 2-blinded observers and adjudicated by a third. (WMS: 1=normal, 2=hypokinetic, 3=akinetic, 4=dyskinetic). WMS improvement was defined as a decrease in WMS ≥ 1, and normalization where WMS = 1 on follow-up. Segmental circumferential strain was derived utilizing DENSE and feature-tracking. A generalized linear mixed model with random effect of subject was constructed and used to account for repeated sampling when investigating predictors of segmental myocardial improvement or normalization RESULTS: At baseline and follow-up, 1416 segments had evaluable data for all parameters. Circumferential strain by DENSE (p < 0.001) and feature-tracking (p < 0.001), extent of oedema (p < 0.001), infarct size (p < 0.001), and microvascular obstruction (p < 0.001) were associates of both improvement and normalization of WMS. Circumferential strain provided incremental predictive value even after accounting for infarct size, extent of oedema and microvascular obstruction, for segmental improvement (DENSE: odds ratio, 95% confidence intervals: 1.08 per -1% peak strain, 1.05-1.12, p < 0.001, feature-tracking: odds ratio, 95% confidence intervals: 1.05 per -1% peak strain, 1.03-1.07, p < 0.001) and segmental normalization (DENSE: 1.08 per -1% peak strain, 1.04-1.12, p < 0.001, feature-tracking: 1.06 per -1% peak strain, 1.04-1.08, p < 0.001). CONCLUSIONS: Circumferential strain provides incremental prognostic value over segmental infarct size in patients post STEMI for predicting segmental improvement or normalization by wall-motion scoring.

Serial imaging after pulmonary embolism and correlation with functional limitation at 12 months: Results of the ELOPE Study.

INTRODUCTION: Risk factors for exercise limitation after acute pulmonary embolism (PE) are unknown. As a planned sub-study of the prospective, multicenter ELOPE (Evaluation of Long-term Outcomes after PE) Study, we aimed to describe the results of serial imaging by computed tomography pulmonary angiography (CTPA) and perfusion scan during 1 year after a first episode of acute pulmonary embolism, and to assess the association between imaging parameters and exercise limitation at 1 year. METHODS: In a prospective cohort study, 100 patients were recruited between June 2010 and February 2013 at five Canadian university-affiliated hospitals. CT pulmonary angiography was performed at baseline and 12 months, perfusion scan at 6 and 12 months, and cardio-pulmonary exercise testing at 1 and 12 months. Imaging parameters included: on CT pulmonary angiography, CT obstruction index (CTO) (% clot burden in the pulmonary vasculature), and on perfusion scan, pulmonary vascular obstruction (PVO) (% perfusion defect). Abnormal cardio-pulmonary exercise test (primary outcome) was defined as percent of predicted peak oxygen uptake (VO2) <80%. RESULTS: Mean (median; SD) CT obstruction index was 28.1% (27.5%; 18.3%) at baseline, 1.2% (0%; 4.3%) at 12 months. Mean (median; SD) pulmonary vascular obstruction was 6.0% (0%; 9.6%) at 6 months, 5.6% (0%; 9.8%) at 12 months. Eighty-six patients had exercise testing at 12 months, and 46.5% had VO2 < 80% predicted. Mean (median; SD) CT obstruction index at 1 year was similar in patients with percent-predicted VO2 peak <80% vs >80% on 1-year cardio-pulmonary exercise testing (1.4% [0%; 5.7%] vs 1.0% [0%; 2.4%]; P = .70). Mean (SD) pulmonary vascular obstruction at 6 and at 12 months was similar in patients with percent-predicted VO2 peak <80% vs >80% (6 months: 5.9% [0%; 10.4%] vs 6.2% [4.5%; 9.0%]; P = .91; 12 months: 5.1% [0%; 10.2%] vs 6.0% [0%; 9.7%]; P = .71). CONCLUSIONS: Imaging findings after pulmonary embolism did not predict exercise limitation. Residual thrombus does not appear to explain long-term functional limitation after pulmonary embolism.

Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial.

BACKGROUND: Patients with angina symptoms and/or signs of ischemia but no obstructive coronary artery disease (INOCA) pose a diagnostic and therapeutic challenge. OBJECTIVES: The purpose of this study was to test whether an interventional diagnostic procedure (IDP) linked to stratified medicine improves health status in patients with INOCA. METHODS: The authors conducted a randomized, controlled, blinded clinical trial of stratified medical therapy versus standard care in patients with angina. Patients with angina undergoing invasive coronary angiography (standard care) were recruited. Patients without obstructive CAD were immediately randomized 1:1 to the intervention group (stratified medical therapy) or the control group (standard care, IDP sham procedure). The IDP consisted of guidewire-based assessment of coronary flow reserve, index of microcirculatory resistance, fractional flow reserve, followed by vasoreactivity testing with acetylcholine. The primary endpoint was the mean difference in angina severity at 6 months (assessed by the Seattle Angina Questionnaire summary score). RESULTS: A total of 391 patients were enrolled between November 25, 2016, and November 12, 2017. Coronary angiography revealed obstructive disease in 206 (53.7%). One hundred fifty-one (39%) patients without angiographically obstructive CAD were randomized (n = 76 intervention group; n = 75 blinded control group). The intervention resulted in a mean improvement of 11.7 U in the Seattle Angina Questionnaire summary score at 6 months (95% confidence interval [CI]: 5.0 to 18.4; p = 0.001). In addition, the intervention led to improvements in the mean quality-of-life score (EQ-5D index 0.10 U; 95% CI: 0.01 to 0.18; p = 0.024) and visual analogue score (14.5 U; 95% CI: 7.8 to 21.3; p < 0.001). There were no differences in major adverse cardiac events at the 6-month follow-up (2.6% controls vs. 2.6% intervention; p = 1.00). CONCLUSIONS: Coronary angiography often fails to identify patients with vasospastic and/or microvascular angina. Stratified medical therapy, including an IDP with linked medical therapy, is routinely feasible and improves angina in patients with no obstructive CAD. (CORonary MICrovascular Angina [CorMicA]; NCT03193294).

Association is not causation: treatment effects cannot be estimated from observational data in heart failure.

Aims: Treatment 'effects' are often inferred from non-randomized and observational studies. These studies have inherent biases and limitations, which may make therapeutic inferences based on their results unreliable. We compared the conflicting findings of these studies to those of prospective randomized controlled trials (RCTs) in relation to pharmacological treatments for heart failure (HF). Methods and results: We searched Medline and Embase to identify studies of the association between non-randomized drug therapy and all-cause mortality in patients with HF until 31 December 2017. The treatments of interest were: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists (MRAs), statins, and digoxin. We compared the findings of these observational studies with those of relevant RCTs. We identified 92 publications, reporting 94 non-randomized studies, describing 158 estimates of the 'effect' of the six treatments of interest on all-cause mortality, i.e. some studies examined more than one treatment and/or HF phenotype. These six treatments had been tested in 25 RCTs. For example, two pivotal RCTs showed that MRAs reduced mortality in patients with HF with reduced ejection fraction. However, only one of 12 non-randomized studies found that MRAs were of benefit, with 10 finding a neutral effect, and one a harmful effect. Conclusion: This comprehensive comparison of studies of non-randomized data with the findings of RCTs in HF shows that it is not possible to make reliable therapeutic inferences from observational associations. While trials undoubtedly leave gaps in evidence and enrol selected participants, they clearly remain the best guide to the treatment of patients.

Disseminated Multi-system Sarcoidosis Mimicking Metastases on 18F-FDG PET/CT.

A 60-year-old female with no significant medical history presented with hematuria. A computed tomography (CT) scan revealed extensive lymphadenopathy with hypodensities in the liver and spleen, and she was referred for an 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/CT (PET/CT) study to assess for malignancy of unknown primary. PET/CT revealed extensive 18F-FDG avid lymphadenopathy as well as innumerable intensely 18F-FDG avid lung, liver and splenic nodules, highly concerning for malignancy. A PET-guided bone marrow biopsy of the posterior superior iliac spine revealed several non-necrotizing, well-formed granulomas, consistent with sarcoidosis. The patient was managed conservatively and remained clinically well over the subsequent 9 years of follow-up.

Effect of digoxin in patients with heart failure and mid-range (borderline) left ventricular ejection fraction.

AIMS: To evaluate the effects of digoxin in patients with the newly described phenotype of heart failure (HF) and mid-range ejection fraction (HFmrEF), attributed to mild left ventricular systolic dysfunction. METHODS AND RESULTS: We carried out a retrospective analysis of the Digitalis Investigation Group (DIG) trial which had 7788 patients available for analysis with a left ventricular ejection fraction (LVEF) ranging between 3% and 85%. We compared the effect of digoxin to placebo in three mutually exclusive groups of patients defined by LVEF category: <40% (HF with reduced LVEF, HFrEF, n = 5874), 40-49% (HFmrEF, n = 1195) and ≥50% (HF with preserved LVEF, HFpEF, n = 719). The primary outcome was the composite of cardiovascular death or HF hospitalisation. Patients with HFmrEF resembled patients with HFrEF, more than those with HFpEF, with respect to age, sex and aetiology but were more like HFpEF patients with respect to blood pressure and the prevalence of hypertension. Event rates in patients with HFmrEF were similar to those in HFpEF and much lower than in HFrEF. Digoxin reduced the primary endpoint in patients with HFrEF, mainly due to reduced HF hospitalisation: the digoxin/placebo hazard ratio (HR) for HF hospitalisation was 0.71 [95% confidence interval (CI) 0.65-0.77]. The digoxin/placebo HR for HF hospitalisation in patients with HFmrEF was 0.80 (95% CI 0.63-1.03) and 0.85 (95% CI 0.62-1.17) in those with HFpEF. The digoxin/placebo HR for the composite of HF death or HF hospitalisation was 0.74 (95% CI 0.68-0.81) in HFrEF, 0.83 (95% CI 0.66-1.05) in HFmrEF and 0.88 (95% CI 0.65-1.19) in HFpEF. CONCLUSIONS: In this study, event rates in patients with HFmrEF were closer to those in HFpEF than HFrEF. Digoxin had most effect on HF hospitalisation in patients with HFrEF, an intermediate effect in HFmrEF, and the smallest effect in HFpEF.

Functional and Exercise Limitations After a First Episode of Pulmonary Embolism: Results of the ELOPE Prospective Cohort Study.

BACKGROUND: We aimed to determine the frequency and predictors of exercise limitation after pulmonary embolism (PE) and to assess its association with health-related quality of life (HRQoL) and dyspnea. METHODS: One hundred patients with acute PE were recruited at five Canadian hospitals from 2010 to 2013. Cardiopulmonary exercise testing (CPET) was performed at 1 and 12 months. Quality of life (QoL), dyspnea, 6-min walk distance (6MWD), residual clot burden (perfusion scan, CT pulmonary angiography), cardiac function (echocardiography), and pulmonary function tests (PFTs) were measured during follow-up. The prespecified primary outcome was percent predicted peak oxygen uptake (Vo2 peak) < 80% at 1-year CPET. RESULTS: At 1 year, 40 of 86 patients (46.5%) had percent predicted Vo2 peak < 80% on CPET, which was associated with significantly worse generic health-related QoL (HRQoL), PE-specific HRQoL and dyspnea scores, and significantly reduced 6MWD at 1 year. Predictors of the primary outcome included male sex (relative risk [RR], 3.2; 95% CI, 1.3-8.1), age (RR, 0.98; 95% CI, 0.96-0.99 per 1-year age increase), BMI (RR 1.1; 95% CI, 1.01-1.2 per 1 kg/m2 BMI increase), and smoking history (RR, 1.8; 95% CI, 1.1-2.9), as well as percent predicted Vo2 peak < 80% on CPET at 1 month (RR, 3.8; 95% CI,1.9-7.2), and 6MWD at 1 month (RR, 0.82; 95% CI, 0.7-0.9 per 30-m increased walking distance). Baseline or residual clot burden was not associated with the primary outcome. Mean PFT and echocardiographic results (pulmonary artery pressure, right and left ventricular systolic function) at 1 year were similarly within normal limits in both patients with exercise limitations and those without such limitations. CONCLUSIONS: Almost half of patients with PE have exercise limitation at 1 year that adversely influences HRQoL, dyspnea, and walking distance. CPET or 6MWD testing at 1 month may help to identify patients with a higher risk of exercise limitation at 1 year after PE. Based on our results, we believe that the deconditioning that occurs after acute PE could underlie this exercise limitation, but we cannot exclude the fact that this may have been present before PE. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01174628; URL: www.clinicaltrials.gov.

Falling Cardiovascular Mortality in Heart Failure With Reduced Ejection Fraction and Implications for Clinical Trials.

OBJECTIVES: This study examined the trends in the relative contributions of cardiovascular and noncardiovascular mortality to total mortality according to use of beta-blockers in clinical trials of patients with heart failure with reduced ejection fraction (HF-REF). BACKGROUND: With the increasingly widespread use of disease-modifying therapies, particularly beta-blockers, in HF-REF, the proportion of patients dying from cardiovascular causes is likely to be decreasing. METHODS: In a systematic review, 2 investigators independently searched online databases to identify clinical trials including >400 patients with chronic heart failure published between 1986 and 2014 and that adjudicated cause of death. Trials were divided into 3 groups on the basis of the proportion of patients treated with a beta-blocker (<33% [low], 33% to 66% [medium], and >66% [high]). Percentages of total deaths adjudicated as cardiovascular or noncardiovascular were calculated by weighted means and weighted standard deviations. Weighted Student t tests were used to compare results between groups. RESULTS: Sixty-six trials met the inclusion criteria with a total of 136,182 patients and 32,140 deaths. There was a sequential increase in the percentage of noncardiovascular deaths with increasing beta-blocker use from 11.4% of all deaths in trials with low beta-blocker use to 19.1% in those with high beta-blocker use (p < 0.001). CONCLUSIONS: In trials of patients with HF-REF, the proportion of deaths adjudicated as cardiovascular has decreased. Cardiovascular mortality, and not all-cause mortality, should be used as an endpoint for trials of new treatments for HF-REF.

Infectious and inflammatory complications of surgical management of cancer patients imaged with 18F-FDG PET/CT: a pictorial essay.

The aim of this pictorial essay was to highlight the usefulness of fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in evaluating incidental infection or inflammation in cancer patients, related to surgical management. A retrospective review of 10,985 consecutive oncologic PET/CTs was done, and nine cases with suspected FDG positive infectious or inflammatory processes were selected for further review. PET/CT helped identify infections and inflammatory processes related to surgical management of cancer patients, define the extent of infection or inflammation, guide the management and, in some cases, evaluate response to therapy.

Spectrum of malignant renal and urinary bladder tumors on 18F-FDG PET/CT: a pictorial essay.

A wide variety of malignant renal and urinary bladder diseases can be detected on (18)F-FDG PET/CT. Although the PET/CT findings are often nonspecific, the aim of this atlas was to demonstrate that the spectrum of renal and urinary bladder malignancy that can be evaluated with PET/CT is much broader than current medical literature would suggest. PET/CT readers and oncologists should be aware of the variety of urological tumor types that can be detected on PET/CT and some of the patterns of (18)F-FDG uptake that can be observed in these cases.

Spectrum of gastric malignancy on 18F-FDG PET/CT: a pictorial essay.

A wide variety of malignant gastric diseases can be detected, staged, and followed on (18)F-FDG PET/CT. Although the PET/CT findings are often nonspecific and some can be seen in certain benign gastric diseases, the aim of this atlas was to demonstrate that the wide histological spectrum of gastric tumors that can be evaluated, staged, and followed with PET/CT is much broader than current medical literature would suggest. PET/CT readers and oncologists should be aware of the utility of PET/CT in these tumors and the imaging characteristics and patterns of (18)F-FDG uptake that can be demonstrated in these cases.

Spectrum of malignant pleural and pericardial disease on FDG PET/CT.

OBJECTIVE: The purpose of this article is to illustrate a wide spectrum of malignant primary and secondary pleural and pericardial diseases imaged with (18)F-FDG PET/CT. CONCLUSION: A wide variety of malignant pleural and pericardial diseases can be detected, staged, and monitored by FDG PET/CT. Although the PET/CT findings are often nonspecific, the aim of this atlas is to show that the spectrum of pleural and pericardial disease that can be evaluated with PET/CT is much broader than current literature would suggest. PET/CT readers and oncologists should be aware of the wide variety of malignancies that can affect the pleura and pericardium and some of the patterns of FDG uptake that can be observed in these cases.

Submandibular salivary gland transfer: a pitfall in head and neck imaging with F-18 FDG PET/CT.

Xerostomia is a significant morbidity of radiation treatment in the management of head and neck cancers. To preserve salivary function, a surgical technique has been developed that involves the transfer of one submandibular gland to the ipsilateral submental space, where it can be shielded during radiation therapy. F-18 FDG PET/CT imaging characteristics of recently or remotely transferred submandibular glands have not been previously described in the literature. We report 2 cases of patients with surgically transferred submandibular glands, which highlight a potential pitfall in the interpretation of PET/CT of the head and neck region in oncologic patients.